Sterol transport through niemann-pick type c proteins from the rnd superfamily

Bjørn Panyella Pedersen, Associate Prof.

Department of Molecular Biology and Genetics, Aarhus University, Denmark

Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis in all eukaryotes. They drive sterol integration into the vacuolar/lysosomal membrane before redistribution to other cellular membranes. My group uses a combination of crystallography, cryo-electronmicroscopy, biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system, NCR1/NPC2, to generate a conceptual framework for sterol membrane integration in eukaryotes. In this system, sterols are transferred between hydrophobic pockets of the small vacuolar protein NPC2 and the membrane-protein NCR1, part of the RND superfamily. After capture by NCR1, the sterols are transferred to the lipid bilayer for integration through a molecular mechanism that is still being elucidated. I will present our recent data which clarifies the role of NPC proteins in this essential eukaryotic pathway.